A Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Assay Identifies Nilotinib as an Inhibitor of Inflammation in Acute Myeloid Leukemia Article Swipe
José Luis Marín‐Rubio
,
Rachel E. Heap
,
María Emilia Dueñas
,
Tiaan Heunis
,
Abeer Dannoura
,
Joseph Inns
,
Jonathan Scott
,
A. John Simpson
,
Helen J. Blair
,
Olaf Heidenreich
,
James M. Allan
,
Jessica E. Watt
,
Mathew P. Martin
,
Barbara Saxty
,
Matthias Trost
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1021/acs.jmedchem.2c00671
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1021/acs.jmedchem.2c00671
Inflammatory responses are important in cancer, particularly in the context of monocyte-rich aggressive myeloid neoplasm. We developed a label-free cellular phenotypic drug discovery assay to identify anti-inflammatory drugs in human monocytes derived from acute myeloid leukemia (AML), by tracking several features ionizing from only 2500 cells using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. A proof-of-concept screen showed that the BCR-ABL inhibitor nilotinib, but not the structurally similar imatinib, blocks inflammatory responses. In order to identify the cellular (off-)targets of nilotinib, we performed thermal proteome profiling (TPP). Unlike imatinib, nilotinib and other later-generation BCR-ABL inhibitors bind to p38α and inhibit the p38α-MK2/3 signaling axis, which suppressed pro-inflammatory cytokine expression, cell adhesion, and innate immunity markers in activated monocytes derived from AML. Thus, our study provides a tool for the discovery of new anti-inflammatory drugs, which could contribute to the treatment of inflammation in myeloid neoplasms and other diseases.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1021/acs.jmedchem.2c00671
- OA Status
- hybrid
- Cited By
- 8
- References
- 100
- Related Works
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- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4295242685Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1021/acs.jmedchem.2c00671Digital Object Identifier
- Title
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A Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Assay Identifies Nilotinib as an Inhibitor of Inflammation in Acute Myeloid LeukemiaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-09-12Full publication date if available
- Authors
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José Luis Marín‐Rubio, Rachel E. Heap, María Emilia Dueñas, Tiaan Heunis, Abeer Dannoura, Joseph Inns, Jonathan Scott, A. John Simpson, Helen J. Blair, Olaf Heidenreich, James M. Allan, Jessica E. Watt, Mathew P. Martin, Barbara Saxty, Matthias TrostList of authors in order
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https://doi.org/10.1021/acs.jmedchem.2c00671Publisher landing page
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://doi.org/10.1021/acs.jmedchem.2c00671Direct OA link when available
- Concepts
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Nilotinib, Myeloid leukemia, Chemistry, Cancer research, Inflammation, Leukemia, Myeloid, Imatinib, Pharmacology, Immunology, MedicineTop concepts (fields/topics) attached by OpenAlex
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8Total citation count in OpenAlex
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2024: 4, 2023: 3, 2022: 1Per-year citation counts (last 5 years)
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100Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works_count | 100 |
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| corresponding_author_ids | https://openalex.org/A5020671002, https://openalex.org/A5000162520 |
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